Nitric oxide scavengers

Abstract

Therapeutic compositions capable of removing excess nitric oxide are provided. The therapeutic compositions include nitronyl nitroxide monoradicals, B12 derivatives, flavonoid derivatives, the like and combinations thereof. The therapeutic compositions can be utilized in a number of suitable applications, such as to prevent or treat intradialytic hypotension during dialysis.

The invention is claimed as follows: 
     
       1. A membrane capable of removing excess nitric oxide, the membrane comprising a modified surface including a ligand attached thereto, the ligand including a nitronyl nitroxide monoradical. 
     
     
       2. The membrane of  claim 1 , wherein the nitronyl nitroxide monoradical is selected from the group consisting of:
 1,3-dihydroxy-2-(2,4-dihydroxyphenyl)-4,4,5,5-tetramethylimidazolidine; 
 1,3-dihydroxy-2-(3,4-dihydroxyphenyl)-4,4,5,5-tetramethylimidazolidine; 
 1,3-dihydroxy-2-(4-pyridyl)-4,4,5,5-tetramethylimidazolidine; 
 1,3-dihydroxy-2-(2-thienyl)-4,4,5,5-tetramethylimidazolidine; 1,3-Dihydroxy-2-(2-furyl)-4,4,5,-tetramethylimidazolidine; and 
 combinations thereof. 
 
     
     
       3. A dialysis solution comprising:
 a composition including a pharmaceutically active agent selected from the group consisting of a nitronyl nitroxide monoradical, a B12 derivative, and combinations thereof, wherein the composition is capable of removing excess nitric oxide. 
 
     
     
       4. The dialysis solution of  claim 3  wherein the nitronyl nitroxide monoradical is selected from the group consisting of:
 1,3-dihydroxy-2-(2,4-dihydroxyphenyl)-4,4,5,5-tetramethylimidazolidine; 
 1,3-dihydroxy-2-(3,4-dihydroxyphenyl)-4,4,5,5-tetramethylimidazolidine; 
 1,3-dihydroxy-2-(4-pyridyl)-4,4,5,5-tetramethylimidazolidine; 
 1,3-dihydroxy-2-(2-thienyl)-4,4,5,5-tetramethylimidazolidine; 1,3-Dihydroxy-2-(2-furyl)-4,4,5,5-tetramethylimidazolidine; and combinations thereof. 
 
     
     
       5. The dialysis solution of  claim 3  wherein the B12 derivative is selected from the group consisting of hydroxocobalamin, cyanocobalamin and combinations thereof. 
     
     
       6. The dialysis solution of  claim 3  wherein the dialysis solution includes a peritoneal dialysis solution. 
     
     
       7. The dialysis solution of  claim 6  wherein the peritoneal dialysis solution includes a plurality of solution parts. 
     
     
       8. A cartridge for removing uremic toxins, the cartridge comprising:
 a bead material having a pharmaceutical agent attached thereto, the pharmaceutical agent comprising a nitronyl nitroxide monoradical, wherein the pharmaceutical agent is capable of removing an excess amount of nitric oxide at a cellular level without inhibiting nitric oxide synthesis. 
 
     
     
       9. The cartridge of  claim 8 , wherein the nitronyl nitroxide monoradical is selected from the group consisting of:
 1,3-dihydroxy-2-(2,4-dihydroxyphenyl)-4,4,5,5-tetramethylimidazolidine; 
 1,3-dihydroxy-2-(3,4-dihydroxyphenyl)-4,4,5,5-tetramethylimidazolidine; 
 1,3-dihydroxy-2-(4-pyridyl)-4,4,5,5-tetramethylimidazolidine; 
 1,3-dihydroxy-2-(2-thienyl)-4,4,5,5-tetramethylimidazolidine; 1,3-Dihydroxy-2-(2-furyl)-4,4,5,5-tetramethylimidazolidine; 
 and combinations thereof.